The overall objectives of this project is to define more clearly the role of insulin and cyclic-3', 5'-nucleotides in the regulation of glycogen metabolism and the functional capacity of leukocytes involved in inflammatory and immunologic responses. The association of hormone-induced changes in cyclic 3'5'-nucleotides and decreased lymphocyte blastogenic responses will be studied as a potential tool to evaluate cell-mediated immune responsiveness. The insulin dependence of glycogen synthetic enzymes of polymorpho-nuclear leukocytes and lymphocytes will be assessed as potential indicators of an altered functional capacity of such cells in the insulin-deficient diabetic state. Experiments will be done to correlate differences in normal and diabetic lymphocyte blastogenic responses with observed differences in cyclic nucleotide metabolism. This will be done by studying the influence of agentsknown to increase cyclic GMP and cyclic AMP. A difference in the sensitivity or dose response characteristics of these cells will be tested with the above agents in order to detect possible altered cell receptor specificity and sensitivity. The chemotactic response and immune reactant stimulation of lysosomal enzyme release of normal and diabetic polymorphonuclear leukocytes will be investigated in the presence of normal and diabetic plasma. The influecne of diabetic plasma and insulin on cyclic-3',5'-nucleotides will be examined in all cases where alteredc chemotaxis and lysosomal enzyme release is observed.